Map of the human heart

Talking with the TAU professor whose team just achieved a biological milestone: 3D-printing a heart using human tissue and vessels.

By ILANA STUTLAND
June 19, 2019 20:31
Map of the human heart

‘OUR HOPE is that we’ll be able to save as many people’s lives as possible.’. (photo credit: NIR KEDAR)

 
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Prof. Tal Dvir is a very cautious person. Even after countless international and local media outlets swooped down upon him, he’s managed to remain calm and collected, with his feet on the ground, despite the hullabaloo surrounding him.

A publication that came out a couple months ago announced that for the first time ever, Dvir’s team has successfully 3D-printed a heart using human tissue and vessels. This took place in Dvir’s lab at Tel Aviv University, but the professor chooses his words very carefully when talking about his project.

“We are still in the preliminary stage,” explains Dvir. “Our excellent progress is critically important, but we are still so far from producing a real heart.” Dvir, 45 – who is the lead researcher of the study from TAU’s School of Molecular Cell Biology and Biotechnology, Department of Materials Science and Engineering, Center for Nanoscience and Nanotechnology and Sagol Center for Regenerative Biotechnology – was shocked by all the commotion surrounding the publication of his study. “I was quite surprised by all the media attention after the study was published. In fact, my students and I were a bit overwhelmed and completely unprepared for all the questions posed by all the international media organizations.”

Dvir has a bachelor’s degree in engineering from Ben-Gurion University of the Negev. “I was lucky enough to join Prof. Smadar Cohen’s lab in my first year of studies,” says Dvir. “She became my mentor. I worked in her lab throughout my undergrad years, and continued there during my doctoral studies, too. That’s where I learned how to do research. We’re still in touch, and she has been a great help to me over the years. I did my post-doctoral work in Boston, and then in 2011, I opened my own lab at Tel Aviv University.”

3D printed heart (Credit: NIR KEDAR)

What was the impetus for your research in this area?
“Well, I was interested in this field first and foremost because heart disease is the leading cause of death in the western world. One in three deaths in the US are due to heart disease. That’s a really scary statistic and I’m at an age when this could happen to me, too. People in need of a heart transplant can wait for years until a suitable match can be located, and most patients die while they’re waiting. What we’re doing is looking 15 years ahead to a time when we’ll be able to create replacement human organs with 3D printers, when we’ll no longer be dependent on donated organs.”

How optimistic are you that you’ll succeed?
“I’m very optimistic, but I’m not making any promises. It’s not a foregone conclusion that the first organ that will be 3D-printed will be a heart, since other organs are much simpler to make, but I do believe that it will happen eventually. We can already 3D-print skin cells and cartilage, which is relatively simple tissue. No one anywhere in the world has succeeded yet in 3D-printing organs. We are the first ones to successfully engineer and print an entire heart – replete with cells, blood vessels, ventricles and chambers. Granted, it’s a very basic heart, but it is proof that our mission is feasible, and so we are forging on. We’re busy researching how to improve the organ and make its cells work correctly and in a synchronized fashion. We need to keep the cells alive for an extended period.”

PROF. DVIR’S TEAM has been carrying out research on this project for three or four years already. “My student researchers and I are seeing positive results every day, and slowly our project is progressing. It’s not like one day we had a surprising breakthrough,” he explains. “Our research results were published all at once, but our progress has been slowly evolving over a long time.”

Have you received any inquiries directly from patients yet?

“Yes, we get phone calls all the time. Every time new findings are published, we are inundated with calls from people all over the globe. And so I need to tell them that actually, we are still very far away from creating a full-size heart that can be transplanted into a human.”

How have you managed to achieve the milestones you’ve already reached?
“Our technology is based on adipose tissue which we excise from human donors. What we do is separate the fat cells from the extracellular matrix (collagen and carbohydrates) and these cells become stem cells, which we then turn into cardiac muscle cells or cells that form blood vessels. We transform the extracellular matrix – the collagen and carbohydrates – into bio-ink. We use the cardiac muscle cells and a different bio-ink and then make a 3D printing according to the model of a real human heart.”

THE HEART-PRINTING project is being financed by the EU and businessman Sami Sagol, one of Tel Aviv University’s main donors. “Sami Sagol has invested a tremendous amount in the Sagol Center for Regenerative Biotechnology, and he is an active partner,” explained Dvir. “I must also commend the incredible work carried out by doctoral student Nadav Nur and Dr. Assaf Shapira. Both of them have spent many more sleepless nights in the lab than I have.”

What are the long-term goals of your project?
“Our hope is that we’ll be able to save as many people’s lives as possible,” says Dvir. “At some point in the future – this could take a while – if we succeed in building personalized hearts, then people will no longer have to wait years for donor organs to become available. Once a sick person is fitted with a heart that works well, their quality of life and life expectancy should improve greatly.” Currently, it takes 2-3 hours to print a small 2 cm. wide heart. “Of course, it will take much more time to print human-sized hearts, which are about the size of your fist.”
“As of now, we haven’t yet succeeded in implanting any of the hearts we’ve printed into a living creature. We need to improve the connectivity between the cells and the electrical activity. Our aim is to carry out research that will help us reach the stage in which a basic heart works properly in the lab. The next stage would be to implant a heart into a small animal, such as a rat or rabbit. Once we succeed at that stage, we will start worrying about how to build a human heart. The field of 3D printing is progressing quickly these days, but tissue engineering is still in its infancy. Research in this field has just begun and we are so excited to be among the first people to engage in this research.”

PROF. TAL DVIR: ‘We are the first ones to successfully engineer and print an entire heart replete with cells, blood vessels, ventricles and chambers.’ (Credit: JACK GUEZ)

Does the fact that you succeeded in 3D printing a heart mean that it will be possible to print other organs, too?
“Theoretically, we should be able to use the same technology to print other organs, too. In addition, using printed organs can also solve the problem of implant rejection, since printed hearts will be made from a patient’s own cells and tissues, and therefore a person’s immune system shouldn’t try to reject the new heart. There are a number of teams around the world currently working on similar projects, and I’m sure the publicity following the publication of our findings will probably pique the interest of biotech companies.”

DESPITE HIS RESERVATIONS, Dvir expressed great satisfaction from his work, as would be expected. “It’s a great feeling to carry out such important research,” confessed Dvir. “On a personal level, I don’t love all the public exposure, but I understand that it’s necessary if we want to advance our research. We’ve achieved positive results in small increments – it’s been an extremely slow process – but we have so much work ahead of us. We haven’t rested for a moment, and we’re always forging ahead. That’s why this benchmark does not feel so extraordinary for me, since we’re always slowly progressing.

“I’ve been involved in this project from day one, so to me this just feels like one more small step. The biggest change for me recently has been talking with the media – it does not come naturally for me and it makes me quite uncomfortable. This is just one of a number of projects we’re working on in my lab, and they’re all extremely exciting. It’s my hope that all of our projects will help people and be beneficial in our lives.”

Translated by Hannah Hochner.


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